Synthesis and Antifungal Activity against Fusarium oxysporum of Some Brassinin Analogs Derived from l-tryptophan: A DFT/B3LYP Study on the Reaction Mechanism

摘要

An efficient methodology to obtain novel antifungal analogs of brassinin >1 is described. Starting from l-tryptophan >2, N,N′-dialkylthiourea >4, 4-[(1H-indol-3-yl)methylene]-2-sulfanylidene-1,3-thiazolidin-5-one >5 and alkyl (2S)-3-(1H-indol-3-yl)-2-{[(alkylsulfanyl)carbonothioyl]amino}propanoate >6 type compounds were obtained as main products in different ratios depending on the reaction conditions via a tandem dithiocarbamate formation and Michael addition reaction. In order to understand the dependence of the reaction conditions on the mechanism pathway, a DFT/B3LYP study was performed. The results suggested the existence of competitive mechanistic routes which involve the presence of an ionic dithiocarbamate intermediate >9. Antifungal activities of all products were then evaluated against Fusarium oxysporum through mycelial growth inhibition using a microscale amended-medium assay. IC50 values were thus determined for each compound. These results showed that >6-related compounds can be considered as promissory antifungal agents.